This invention relates to the diagnosis and/or treatment of a patient's heart and particularly to the delivery of therapeutic or diagnostic devices and agents to a patient's heart tissue from within the patient's heart chamber.
Coronary artery disease affects the lives of millions of patients worldwide. Many therapies are available for atherosclerosis, including CABG surgery to bypass blocked arteries, PTCA interventions to attempt to restore patency, stents that also attempt to maintain patency, atherectomy to remove the collected plaque, and a number of pharmacological approaches that attempt to reduce the effects of narrowing of vessel lumens, by the stenosis, by reducing the amount of plaque or by altering the hemodynamic characteristics of the patient's blood. While the aforesaid procedures provide well known clinical improvements, none provide a fully satisfactory long term therapy. The presently available pharmacological therapies are of limited value. Ideally, a non-invasive pharmacological or genetic therapy would facilitate reperfusion of the ischemic myocardium, either by restoring patency, or by creating new blood vessels to supply the ischemic region with additional oxygenated blood.
A number of different substances and techniques are known for attempting to treat coronary artery disease by the administration of a therapeutic substance to a patient. One common method of administration is systemic administration. For example, EPO Application EP 314105 discloses the oral administration or intramuscular injection of an "angiogenesis enhancer." U.S. Pat. No. 5,480,975 discloses treating hypoxic tissue damage by local or topical administration of a transition metal compound to induce VEGF expression, either by local administration or topical application. The indirect nature of these routes of administration are generally less desirable and not universally applicable to all forms of substances that might be used to treat ischemic myocardium.
Using a catheterization procedure to deliver a substance to the vessels in the vicinity of the stenosis is also known. For example, PCT Application WO 9723256 discloses the percutaneous delivery of an angiogenic factor to a vessel wall through the lumen of a catheter. The distal end of the catheter is provided with infusion ports that engage the vessel wall when the catheter is expanded, and infusion may be enhanced by providing needles or other penetrating elements. U.S. Pat. No. 5,681,278 discloses treating vascular thrombosis and angioplasty restenosis by administering a bioactive agent to an extravascular treatment site, particularly introducing such an agent proximally adjacent to the exterior of a coronary artery. U.S. Pat. No. 5,698,531 discloses site specific installation of cells or the transformation of cells by delivering proteins by catheterization to discrete blood vessel segments wherein the agent is situated on the walls of the blood vessel or perfused in the tissue of the vessel. U.S. Pat. No. 5,523,092 discloses an indwelling catheter for localized delivery of a substance into a tissue conduit without disrupting the fluid flow. U.S. Pat. No. 5,244,460 discloses the intracoronary arterial delivery of a blood vessel growth promoting peptide periodically over several days. None of these references, however, address the provision of a substance directly into the myocardial tissue.
Recent advances in biotechnology have shown great promise for treating coronary artery disease. In Circulation 1998, 97:645-650, Schumacher et al. report treating coronary heart diseases using human growth factor FGF-I (basic fibroblast growth factor) to induce neoangiogenesis in ischemic myocardium. The FGF-I was administered during a CABG procedure by injection into the myocardium distal to the IMA/LAD anastamosis and close to the LAD. The results reported demonstrate the efficacy of FGF-I treatment. However, administration by direct injection during surgery is less than optimal because it is as invasive to the patient as a CABG procedure. In addition, at least one fibroblast growth factor has also been delivered using a microparticle carrier delivered to an artery via a catheter in a non-ischemic model, as reported in Nature Biotechnology 1998; 16:134 and 159-160. The intra-arterial delivery of microparticles produced positive results, but was chosen so that the surrounding tissue would be undamaged. The article indicates that noninvasive techniques to deliver genes into peripheral ischemic myocardium tissue are presently unavailable.
Targeted delivery of therapeutic or diagnostic devices and /or agents is a desirable but often difficult task. For therapeutic and diagnostic devices the advantages include shorter and less traumatic procedures and for therapeutic and diagnostic agents the benefits include more efficient use of the agent and the limitation of the agent action to a desired region. Whether the delivery of a therapeutic or diagnostic device to a desired region of a patient's heart tissue from within the heart chamber thereof is successful and efficient is frequently the result of the physician's skill which can vary considerably from physician to physician and from day to day with the same physician. Accurate delivery of various substances to the tissue of a patient's heart wall can be a function of the same physician skill. Additionally, successful and effective substance delivery can also be a function of minimizing systemic loss, keeping the substance within the desired region, timing and ensuring a sufficient quantity of substance in the desired area for sufficient period of time to achieve the desired therapeutic or diagnostic effect.
Copending application Ser. No. 08/483,512, filed on Jun. 7, 1995, entitled THERAPEUTIC AND DIAGNOSTIC AGENT DELIVERY, describes a method and system for delivering a therapeutic or diagnostic agent by first forming a channel in a heart wall from within a heart chamber defined by the wall and then delivering or depositing the agent within the channel. Reference is made to the use of a laser to form the channel, particularly in conjunction with a transmyocardial revascularization procedure. The application (Ser. No. 08/483,512) is hereby incorporated herein by reference in its entirety. Agents described in Ser. No. 08/483,512 included vascular endothelial growth factor (VEGF), acidic and basic fibroblast growth factors (aFGF, bFGF), angiogenin, nitric oxide, prostaglandin, prostaglandin synthase and other prostaglandin synthetic enzymes and isoforms of superoxide dismutase and other antioxidant proteins.
Coronary artery disease is also successfully treated by transmyocardial revascularization (TMR) alone, using methods and apparatus such as those disclosed in U.S. Pat. Nos. 5,380316, 5,389,096 and 5,54,152. Using intraoperative, minimally invasive or percutaneous techniques, energy is delivered directly to the myocardium in the ischemic area and as a result, a focal injury occurs. This focal injury is typically in the form of a small "channel" formed by a laser. It is believed that the focal injury acts to stimulate subsequent neovasculogenesis. Moreover, in addition to the reperfusion of the ischemic region, there is evidence that the disruption of certain afferent nerves in the tissue and other effects provides acute and chronic reduction in angina pain.
Suitable means for creating a site for angiogenesis were referenced in copending application Ser. No. 08/078,443, filed on Jun. 15, 1993 (Aita et al.), which is incorporated herein in its entirety. The application describes an intravascular system for myocardial revascularization which is introduced percutaneously into a peripheral artery and advanced through the patient's arterial system into the left ventricle of the patient's heart. The procedure affects only the endocardium and the myocardium from within the left ventricle. This procedure eliminates the need of the prior intraoperative procedures to open the chest cavity and to penetrate through the entire heart wall in order to form the channel through the endocardium into the myocardium.
While the percutaneous method and system for introducing therapeutic and diagnostic agents into a patient's heart wall as described in Ser. No. 08/483,512 represented a substantial advance, one of the difficulties with the procedure was that it was difficult to ensure delivery of all of the agent into the channel and keeping the agent within the channel for a sufficient period until the desired therapeutic or diagnostic affect occurred. There exists, therefore, a need for improved apparatus and improved techniques that will permit the adjunctive delivery of substances into localized areas within the myocardium efficaciously, efficiently and in a manner that can enjoy widespread adoption by cardiac surgeons and interventional cardiologists. There also exists a long felt, yet unsolved need for methods and apparatus that permit the localized introduction of a substance into the myocardium directly, either during an intraoperative procedure or percutaneously. What has been needed is an improved delivery system and method for delivering a therapeutic or diagnostic device or agent into heart tissue from within the patient's heart chamber, particularly to provide access to all or substantially all of the endocardial surface from within the heart chamber for delivery of such agents and devices. The present invention satisfies these and other needs.